Nature aging最新文献_第10页

Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline 蛋白质组学确定了感染后脑萎缩和认知能力下降的潜在免疫驱动因素。

IF 17

Nature aging Pub Date : 2024-08-14 DOI: 10.1038/s43587-024-00682-4

Michael R. Duggan, Zhongsheng Peng, Pyry N. Sipilä, Joni V. Lindbohm, Jingsha Chen, Yifei Lu, Christos Davatzikos, Guray Erus, Timothy J. Hohman, Shea J. Andrews, Julián Candia, Toshiko Tanaka, Cassandra M. Joynes, Chelsea X. Alvarado, Mike A. Nalls, Jenifer Cordon, Gulzar N. Daya, Yang An, Alexandria Lewis, Abhay Moghekar, Priya Palta, Josef Coresh, Luigi Ferrucci, Mika Kivimäki, Keenan A. Walker

{"title":"Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline","authors":"Michael R. Duggan, Zhongsheng Peng, Pyry N. Sipilä, Joni V. Lindbohm, Jingsha Chen, Yifei Lu, Christos Davatzikos, Guray Erus, Timothy J. Hohman, Shea J. Andrews, Julián Candia, Toshiko Tanaka, Cassandra M. Joynes, Chelsea X. Alvarado, Mike A. Nalls, Jenifer Cordon, Gulzar N. Daya, Yang An, Alexandria Lewis, Abhay Moghekar, Priya Palta, Josef Coresh, Luigi Ferrucci, Mika Kivimäki, Keenan A. Walker","doi":"10.1038/s43587-024-00682-4","DOIUrl":"10.1038/s43587-024-00682-4","url":null,"abstract":"Infections have been associated with the incidence of Alzheimer disease and related dementias, but the mechanisms responsible for these associations remain unclear. Using a multicohort approach, we found that influenza, viral, respiratory, and skin and subcutaneous infections were associated with increased long-term dementia risk. These infections were also associated with region-specific brain volume loss, most commonly in the temporal lobe. We identified 260 out of 942 immunologically relevant proteins in plasma that were differentially expressed in individuals with an infection history. Of the infection-related proteins, 35 predicted volumetric changes in brain regions vulnerable to infection-specific atrophy. Several of these proteins, including PIK3CG, PACSIN2, and PRKCB, were related to cognitive decline and plasma biomarkers of dementia (Aβ42/40, GFAP, NfL, pTau-181). Genetic variants that influenced expression of immunologically relevant infection-related proteins, including ITGB6 and TLR5, predicted brain volume loss. Our findings support the role of infections in dementia risk and identify molecular mediators by which infections may contribute to neurodegeneration. This study reveals how infections that increase long-term dementia risk can contribute to longitudinal brain volume loss and regulate immunological proteins in plasma, and which of these proteins may drive infection-specific neurodegeneration.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 9","pages":"1263-1278"},"PeriodicalIF":17.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00682-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nonlinear dynamics of multi-omics profiles during human aging 人类衰老过程中多组学特征的非线性动态变化。

IF 17

Nature aging Pub Date : 2024-08-14 DOI: 10.1038/s43587-024-00692-2

Xiaotao Shen, Chuchu Wang, Xin Zhou, Wenyu Zhou, Daniel Hornburg, Si Wu, Michael P. Snyder

{"title":"Nonlinear dynamics of multi-omics profiles during human aging","authors":"Xiaotao Shen, Chuchu Wang, Xin Zhou, Wenyu Zhou, Daniel Hornburg, Si Wu, Michael P. Snyder","doi":"10.1038/s43587-024-00692-2","DOIUrl":"10.1038/s43587-024-00692-2","url":null,"abstract":"Aging is a complex process associated with nearly all diseases. Understanding the molecular changes underlying aging and identifying therapeutic targets for aging-related diseases are crucial for increasing healthspan. Although many studies have explored linear changes during aging, the prevalence of aging-related diseases and mortality risk accelerates after specific time points, indicating the importance of studying nonlinear molecular changes. In this study, we performed comprehensive multi-omics profiling on a longitudinal human cohort of 108 participants, aged between 25 years and 75 years. The participants resided in California, United States, and were tracked for a median period of 1.7 years, with a maximum follow-up duration of 6.8 years. The analysis revealed consistent nonlinear patterns in molecular markers of aging, with substantial dysregulation occurring at two major periods occurring at approximately 44 years and 60 years of chronological age. Distinct molecules and functional pathways associated with these periods were also identified, such as immune regulation and carbohydrate metabolism that shifted during the 60-year transition and cardiovascular disease, lipid and alcohol metabolism changes at the 40-year transition. Overall, this research demonstrates that functions and risks of aging-related diseases change nonlinearly across the human lifespan and provides insights into the molecular and biological pathways involved in these changes. Understanding the molecular changes underlying aging is important for developing biomarkers and healthy aging interventions. In this study, the authors used comprehensive multi-omics data to reveal nonlinear molecular profiles across chronological ages, highlighting two substantial variations observed around ages 40 and 60, which are linked to increased disease risks.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 11","pages":"1619-1634"},"PeriodicalIF":17.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43587-024-00692-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring how APOE ε4 increases Alzheimer’s disease risk in women 探索 APOE ε4 如何增加女性患阿尔茨海默病的风险

IF 17

Nature aging Pub Date : 2024-08-12 DOI: 10.1038/s43587-024-00698-w

George Andrew S. Inglis

引用次数: 0

Real-life intrinsic capacity screening data from the ICOPE-Care program 来自 ICOPE-Care 计划的真实内在能力筛选数据。

IF 17

Nature aging Pub Date : 2024-08-09 DOI: 10.1038/s43587-024-00684-2

Philipe de Souto Barreto, Emmanuel Gonzalez-Bautista, Heike A. Bischoff-Ferrari, Vitor Pelegrim de Oliveira, Renato Gorga Bandeira de Mello, Sandrine Andrieu, Caroline Berbon, Neda Tavassoli, John R. Beard, Yves Rolland, Maria Eugenia Soto Martín, Bruno Vellas

{"title":"Real-life intrinsic capacity screening data from the ICOPE-Care program","authors":"Philipe de Souto Barreto, Emmanuel Gonzalez-Bautista, Heike A. Bischoff-Ferrari, Vitor Pelegrim de Oliveira, Renato Gorga Bandeira de Mello, Sandrine Andrieu, Caroline Berbon, Neda Tavassoli, John R. Beard, Yves Rolland, Maria Eugenia Soto Martín, Bruno Vellas","doi":"10.1038/s43587-024-00684-2","DOIUrl":"10.1038/s43587-024-00684-2","url":null,"abstract":"The Integrated Care for Older People (ICOPE) program is a healthcare pathway that uses a screening test for intrinsic capacity (IC) as its entry point. However, real-life data informing on how IC domains cluster and change over time, as well as their clinical utility, are lacking. Using primary healthcare screening data from more than 20,000 French adults 60 years of age or older, this study identified four clusters of IC impairment: ‘Low impairment’ (most prevalent), ‘Cognition+Locomotion+Hearing+Vision’, ‘All IC impaired’ and ‘Psychology+Vitality+Vision’. Compared to individuals with ‘Low impairment’, those in the other clusters had higher likelihood of having frailty and limitations in both activities of daily living (ADL) and instrumental activities of daily living (IADL), with the strongest associations being observed for ‘All IC impaired’. This study found that ICOPE screening might be a useful tool for patient risk stratification in clinical practice, with a higher number of IC domains impaired at screening indicating a higher probability of functional decline. The Integrated Care for Older People (ICOPE) program was developed to promote a function-centered and individualized approach to healthy aging, but it is not yet widely implemented. In this study, de Souto Barreto et al. used early-stage ICOPE data collected in primary healthcare from more than 20,000 older adults to characterize patterns of intrinsic capacity impairment and associated odds of frailty and disability.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 9","pages":"1279-1289"},"PeriodicalIF":17.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Decoding the phenotypic mosaic of aging 解码衰老的表型镶嵌。

IF 17

Nature aging Pub Date : 2024-08-09 DOI: 10.1038/s43587-024-00686-0

Liang-Kung Chen

引用次数: 0

Age-associated clonal B cells drive B cell lymphoma in mice 与年龄相关的克隆 B 细胞会诱发小鼠 B 细胞淋巴瘤。

IF 17

Nature aging Pub Date : 2024-08-08 DOI: 10.1038/s43587-024-00671-7

José P. Castro, Anastasia V. Shindyapina, Alessandro Barbieri, Kejun Ying, Olga S. Strelkova, João A. Paulo, Alexander Tyshkovskiy, Rico Meinl, Csaba Kerepesi, Anna P. Petrashen, Marco Mariotti, Margarita V. Meer, Yan Hu, Alexander Karamyshev, Grigoriy Losyev, Mafalda Galhardo, Elsa Logarinho, Artur A. Indzhykulian, Steven P. Gygi, John M. Sedivy, John P. Manis, Vadim N. Gladyshev

{"title":"Age-associated clonal B cells drive B cell lymphoma in mice","authors":"José P. Castro, Anastasia V. Shindyapina, Alessandro Barbieri, Kejun Ying, Olga S. Strelkova, João A. Paulo, Alexander Tyshkovskiy, Rico Meinl, Csaba Kerepesi, Anna P. Petrashen, Marco Mariotti, Margarita V. Meer, Yan Hu, Alexander Karamyshev, Grigoriy Losyev, Mafalda Galhardo, Elsa Logarinho, Artur A. Indzhykulian, Steven P. Gygi, John M. Sedivy, John P. Manis, Vadim N. Gladyshev","doi":"10.1038/s43587-024-00671-7","DOIUrl":"10.1038/s43587-024-00671-7","url":null,"abstract":"Although cancer is an age-related disease, how the processes of aging contribute to cancer progression is not well understood. In this study, we uncovered how mouse B cell lymphoma develops as a consequence of a naturally aged system. We show here that this malignancy is associated with an age-associated clonal B cell (ACBC) population that likely originates from age-associated B cells. Driven by c-Myc activation, promoter hypermethylation and somatic mutations, IgM+ ACBCs clonally expand independently of germinal centers and show increased biological age. ACBCs become self-sufficient and support malignancy when transferred into young recipients. Inhibition of mTOR or c-Myc in old mice attenuates pre-malignant changes in B cells during aging. Although the etiology of mouse and human B cell lymphomas is considered distinct, epigenetic changes in transformed mouse B cells are enriched for changes observed in human B cell lymphomas. Together, our findings characterize the spontaneous progression of cancer during aging through both cell-intrinsic and microenvironmental changes and suggest interventions for its prevention. Castro, Shindyapina et al. explore how aging promotes B cell lymphoma in mice, identifying a population of age-associated clonal B cells that expands through mutation, c-Myc activation and epigenetic alterations to drive age-associated malignancy.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 10","pages":"1403-1417"},"PeriodicalIF":17.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Blocking IL-11 improves healthspan and lifespan in mice 阻断 IL-11 可改善小鼠的健康和寿命。

IF 17

Nature aging Pub Date : 2024-08-08 DOI: 10.1038/s43587-024-00699-9

Hannah Walters

引用次数: 0

Multiorgan biological age shows that no organ system is an island 多器官生物年龄表明，任何器官系统都不是一座孤岛。

IF 17

Nature aging Pub Date : 2024-08-02 DOI: 10.1038/s43587-024-00690-4

引用次数: 0

Maternal age enhances purifying selection on pathogenic mutations in complex I genes of mammalian mtDNA 母体年龄增强了对哺乳动物mtDNA I复合基因致病突变的纯化选择。

IF 17

Nature aging Pub Date : 2024-07-29 DOI: 10.1038/s43587-024-00672-6

Yanfei Ru, Xiaoling Deng, Jiatong Chen, Leping Zhang, Zhe Xu, Qunyu Lv, Shiyun Long, Zijian Huang, Minghua Kong, Jing Guo, Min Jiang

{"title":"Maternal age enhances purifying selection on pathogenic mutations in complex I genes of mammalian mtDNA","authors":"Yanfei Ru, Xiaoling Deng, Jiatong Chen, Leping Zhang, Zhe Xu, Qunyu Lv, Shiyun Long, Zijian Huang, Minghua Kong, Jing Guo, Min Jiang","doi":"10.1038/s43587-024-00672-6","DOIUrl":"10.1038/s43587-024-00672-6","url":null,"abstract":"Mitochondrial diseases, caused mainly by pathogenic mitochondrial DNA (mtDNA) mutations, pose major challenges due to the lack of effective treatments. Investigating the patterns of maternal transmission of mitochondrial diseases could pave the way for preventive approaches. In this study, we used DddA-derived cytosine base editors (DdCBEs) to generate two mouse models, each haboring a single pathogenic mutation in complex I genes (ND1 and ND5), replicating those found in human patients. Our findings revealed that both mutations are under strong purifying selection during maternal transmission and occur predominantly during postnatal oocyte maturation, with increased protein synthesis playing a vital role. Interestingly, we discovered that maternal age intensifies the purifying selection, suggesting that older maternal age may offer a protective effect against the transmission of deleterious mtDNA mutations, contradicting the conventional notion that maternal age correlates with increased transmitted mtDNA mutations. As collecting comprehensive clinical data is needed to understand the relationship between maternal age and transmission patterns in humans, our findings may have profound implications for reproductive counseling of mitochondrial diseases, especially those involving complex I gene mutations. Mitochondrial DNA mutations are subject to purifying selection in the female germline, limiting the transmission of pathogenic variants. In this study, the authors used two mouse models that harbor pathogenic mutations in mitochondrial complex I and observed that maternal age intensifies purifying selection processes.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"4 9","pages":"1211-1230"},"PeriodicalIF":17.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

mTOR links nutrients, inflammaging and lifespan mTOR 将营养、炎症和寿命联系在一起。

IF 17

Nature aging Pub Date : 2024-07-26 DOI: 10.1038/s43587-024-00681-5

Helena M. Cochemé, Jesús Gil

引用次数: 0